title: Norovirus binding to intestinal epithelial cells is independent of histo-blood group antigens.
abstract: Human noroviruses (NoVs) are a major cause of non-bacterial gastroenteritis. Although histo-blood group antigens (HBGAs) have been implicated in the initial binding of NoV, the mechanism of that binding before internalization is not clear. To determine the involvement of NoVs and HBGAs in cell binding, we examined the localization of NoV virus-like particles (VLPs) and HBGAs in a human intestinal cell line and the human ileum biopsy specimens by immunofluorescence microscopy. The localizations of Ueno 7k VLPs (genogroup II.6) and each HBGA (type H1-, H2- and Le(b)-HBGAs) on the human intestinal cell line, Caco-2, were examined by confocal laser-scanning microscopy. To explore any interactions of NoVs and HBGAs in vivo, fresh biopsy specimens from human ileum were directly incubated with NoV VLPs and examined by immunofluorescence microscopy. We found that VLP binding depended on the state of cell differentiation, but not on the presence of HBGAs. In differentiated Caco-2 cells, we detected no type H1 HBGAs, but VLPs bound to the cells anyway. We incubated fresh biopsies of human ileum directly with VLPs, a model that better replicates the in vivo environment. VLPs mainly bound epithelial cells and goblet cells. Although the incubations were performed at 4°C to hinder internalization, VLPs were still detected inside cells. Our results suggest that VLPs utilize molecule(s) other than HBGAs during binding and internalization into cells.
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Musashi-murayama, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Murakami
authors.forename: Chie
authors.initials: C
authors.lastname: Kurihara
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Oka
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimoike
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Fujii
authors.forename: Reiko
authors.initials: R
authors.lastname: Takai-Todaka
authors.forename: YoungBin
authors.initials: Y
authors.lastname: Park
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Matsuda
authors.forename: Ryota
authors.initials: R
authors.lastname: Hokari
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Katayama
mesh_terms: D001789:Blood Group Antigens / Q000378:metabolism*; D018938:Caco-2 Cells; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D029322:Norovirus / Q000502:physiology*; D014771:Virion / Q000502:physiology; D053585:Virus Attachment
chemical_list: D001789:Blood Group Antigens